PR-619 (2645-32-1) is a nonselective, reversible inhibitor of cysteine-reactive deubiquitinating enzymes (DUBs; 5-20 μM)1. PR-619 is highly useful for preserving ubiquitinated proteins during cell lysis. DUBs become unregulated in cell lysates and will act quickly to deubiquitinate proteins of interest during cell lysis. To preserve maximum amounts of ubiquitinated protein, include PR-619 (50-100 μM) in lysis buffers. PR-619 is also useful for interrogating the role of DUBs in intact cell systems2, and treatment of cells results in an overall accumulation of ubiquitinated proteins and many other phenotypes.
PR-619 has been used:
- as a component of lysis buffer and also as a deubiquitinase inhibitor to treat proteins derived from SILAC-labeled Jurkat cells
- as a pan-deubiquitinase inhibitor to study its effect on adenoassociated virus (AAV) transduction
- in radioimmunoprecipitation assay buffer (RIPA) buffer used for ubiquitination assays
PR 619 is a broad-range DUB inhibitor. A selective and general inhibitior of cellular DUB activity without direct impairment of proteasomal proteolysis. Used in the preparation of thiazolopyridines an
d bisthiazolopyridines.
PR-619 is a cell permeable broad spectrum deubiquitylating enzymes (DBUs) inhibitor. PR-619 induces the accumulation of polyubiquitylated proteins in cells without directly affecting proteasome activity.
PR-619 (10 mg/kg/day) enhances the antitumor effect of Cisplatin on a Cisplatin-Na ve and Cisplatin-resistant UC Xenograft of nude mice[4].
| Animal Model: | Nude mice[4]. |
| Dosage: | 10 mg/kg/day (Cisplatin combined). |
| Administration: | Intraperitoneally. |
| Result: | Enhanced the antitumor effect of Cisplatin. |
PR-619 is a small-molecule inhibitor that displays broad specificity toward several deubiquitylating enzymes, including members of the ubiquitin specific protease and the ubiquitin C-terminal hydrolase subfamilies. The ubiquitin proteasome system involves protein ubiquitination by ubiquitinating enzymes followed by proteasomal degradation; the process is reversed by cysteine proteases known as deubiquitinating enzymes that cleave ubiquitin from ubiquitin-conjugated proteins. PR-619 treatment of cells resulted in the accumulation of polyubiquitinated proteins and was not related to any deficiency in proteasome activity. Likewise, PR-619 treatment of an oligodendroglial cell line led to the buildup of protein aggregates near the microtubule network and increased expression of heat shock proteins associated with the cellular stress response. Protein deubiquitination is related to the development of cisplatin-resistant metastatic bladder urothelial carcinoma in patients; PR-619 treatment was shown to relieve chemoresistance in urothelial carcinoma cells and in a mouse xenograft model.
[1] MIKAEL ALTUN. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes.[J]. Chemistry & biology, 2011: 1401-1412. DOI:
10.1016/j.chembiol.2011.08.018[2] VERONIKA SEIBERLICH . The small molecule inhibitor PR-619 of deubiquitinating enzymes affects the microtubule network and causes protein aggregate formation in neural cells: Implications for neurodegenerative diseases[J]. Biochimica et biophysica acta. Molecular cell research, 2012, 1823 11: Pages 2057-2068. DOI:
10.1016/j.bbamcr.2012.04.011
